A large Spanish study suggests an association between obstructive sleep apnoea (OSA) and the development of cancer in men younger than age 65.

But the researchers say the age and gender findings should be interpreted cautiously since the smaller number of individuals in each age and gender subgroup may have decreased the power to detect relevant associations. Nonetheless, they say, the associations found deserve further study.

Intermittent hypoxia, one of the most specific hallmarks of OSA, reportedly plays an important role in tumour formation and progression, Dr Francisco Campos-Rodríguez, of the Sleep-Disordered Breathing Unit at Hospital de Valme, Sevilla, Spain, noted.

"However, despite sharing this pathophysiological pathway, a possible association between OSA and the risk of cancer occurrence had not been previously assessed in human cohorts," he said.

He also noted that a recent study by the Spanish Sleep Network showed that when mice were subjected to an intermittent hypoxia pattern mimicking OSA, the growth rate of melanoma tumours was twice that in control animals who were not subjected to hypoxia. The mice subjected to intermittent hypoxia also showed more pulmonary metastases than the control group.

These findings prompted the researchers to perform a multicenter study in a large sleep cohort to investigate whether OSA is associated with increased cancer incidence in humans.

A likely link between OSA and cancer

According to an online paper in the American Journal of Respiratory and Critical Care Medicine, they analysed 4 910 individuals who were assessed for OSA suspicion in seven Spanish teaching hospitals, and who were followed for 4.5 years.

"We found an increased cancer incidence (that is, occurrence of a new cancer) in OSA patients exhibiting nocturnal hypoxia as compared with those who did not experience nocturnal hypoxia, independently of several potential confounders such as age, gender, obesity, smoking habit and alcohol intake," Dr Campos-Rodríguez said.

It appears that the longer a patient with OSA spends with low night time oxygen levels, the greater the risk of developing a cancer.

"For example," Dr Campos-Rodríguez said, "compared with patients who spent <1.2% of the night time with low oxygen levels (defined as an oxygen saturation <90%), those who spent >12% of the time with low oxygen levels (oxygen saturation <90%) had more than twice the risk of having a cancer during the follow-up period."

The fact that the oximetric parameters were better predictors of cancer incidence than the apnoea-hypopnoea index, "underscores the hypothesis that hypoxia could be the most likely pathological link between OSA and cancer," Dr Campos-Rodríguez noted.

More work needed

The association between OSA and cancer incidence seemed to be limited to men younger than 65 years; the association wasn't seen in women or elderly patients (>65 years), but again, this finding needs to be interpreted cautiously. It can't be ruled out that the lack of association between OSA and cancer incidence in women and those over 65 may be due to lack of power, the researchers say.

More work, they say, is needed to investigate whether a specific cancer location or subtype is more likely to be associated with OSA and the potential role of continuous positive airway treatment (CPAP) in this relationship.

"CPAP is the treatment of choice for OSA patients. This treatment avoids upper airway collapse and its consequences, including intermittent hypoxia. Unfortunately, we did not assess the effect of CPAP treatment in our cohort," Dr Campos-Rodríguez said. "Therefore, although one may speculate that if CPAP avoids intermittent hypoxia associated with OSA, it would possibly have a protective effect against this outcome, whether CPAP reduces cancer incidence in OSA patients needs to be investigated."

The study was supported by the Spanish Respiratory Society. The authors have no relevant disclosures.

Ask the Expert

Dr Alison Bentley is a general practitioner who has consulted in sleep medicine and sleep disorders, in both adults and children of all ages, for almost 30 years. She also researches and publishes on a number of sleep-related topics both in formal research journals and lay publications including as editor of Sleep Matters, an educational newsletter on sleep disorders for doctors.

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